PB2413: SALVAGE THERAPY WITH VENETOCLAX AND A HYPOMETHYLATING AGENT FOR PATIENTS WITH AML RELAPSE AFTER ALLOGENEIC STEM CELL TRANSPLANTATION
Authors: Inna Shaforostova, Julia Marx, Simon Call, Matthias Peter Floeth, Eva Esseling, Christian Reicherts, Joern Christian Albring, Jan-Henrik Mikesch, Christoph Schliemann, Georg Lenz, Matthias Stelljes
Journal: HemaSphere (2023)

Topic: 22. Stem cell transplantation - Clinical Background: Combination therapies of venetoclax with the hypomethylating agents (HMA) azacitidine (AZA) or decitabine (DAC) as first-line therapy in elderly or unfit patients with acute myeloid leukemia (AML) have shown promising efficacy. Preliminary cohort studies in patients (pts) with relapsed or refractory AML reported overall response rates (ORR) of 30-50%. In contrast, outcome data in pts treated with HMA/VEN for relapse after allogeneic stem cell transplantation (allo-HCT) are limited. Aims: In this retrospective single center cohort study we analyzed treatment outcome and toxicity in patients treated with HMA/VEN for post-transplant relapse of AML. Methods: Between August 2019 and March 2022, pts initially diagnosed and transplanted with AML (17 pts), MDS (4 pts), or CMML (1 patient) relapsed with AML after allo-HCT and were treated with HMA/VEN. Post-transplant relapse was defined as re-occurrence of ≥ 5% blasts in bone marrow (BM) and/ or extramedullary disease manifestations for pts initially diagnosed with AML or ≥ 20% BM blasts for pts who were initially diagnosed with MDS or CMML. Responses to HMA/VEN were defined according to European LeukemiaNet (ELN) 2022 risk definitions for BM relapse and according RECIST 1.1 criteria for extramedullary relapse. Results: Median age of the 13 male and 9 female pts was 60 years (range 21-71 years). According to ELN 2022 risk classification 9 pts had an adverse risk, 7 pts had an intermediate risk and 1 patient had a favorable risk. 4 pts had received two allo-HCTs. Median time to relapse after last allo-HCT was 9 months (range 2-54 months). 8 pts had an isolated extramedullary relapse and 14 pts a leukemic relapse with a median (range) BM blast count of 30% (5-90%). In 12 pts HMA/VEN was the first salvage therapy after allo-HCT. 9 pts received one and 1 patient received two lines of previous salvage therapies before HMA/VEN treatment. Prior salvage therapies consisted of gilteritinib (2 pts), AZA monotherapy (4 patients), AZA in combination with lenalidomide (3 pts), or an experimental therapy within a clinical trial (2 pts). Before relapse, 7 pts had received a preemptive treatment with donor lymphocyte infusion (DLI) for impending relapse diagnosed by reappearance/ increasing measurable residual disease and/ or decreasing donor cell chimerism. VEN was combined with AZA in 21 pts and with DAC in 1 patient. 3 pts received DLI in CR after AZA/VEN. The median (range) number of cycles of HMA/VEN was 2 (1-5). Neutropenia occurred in all pts (CTC grade IV in 21 pts). 15 pts had CTC grade 4 thrombocytopenia and 17 patients required transfusion of erythrocytes and/or thrombocytes. Due to CTC grade 3/4 infections, hospital admission was necessary in 13 pts (59%). The ORR was 27% (3 pts with complete remission and 3 pts with partial remission). In first salvage, ORR was 42%, in later salvage lines 10% (p n.s.). Median follow-up after therapy with HMA/VEN was 4 months (range 1-27 months). At last follow-up, 17 patients (77%) had died. Estimated median overall survival (OS) was 3.3 months (95% CI, 4.1-12.3). Median OS of patients with HMA/VEN was 3.3 months for first salvage and 2.8 months in later salvage lines (p n.s.). Summary/Conclusion: Our data are comparable with outcome data of pts relapsing with AML after allo-HCT and treated with HMA +/- DLI. The low response rates in our cohort can be explained, at least in part, by pretreatment with HMA before or after transplantation. Prospective studies are urgently needed to define the role of post-transplant VEN-based salvage therapies. Keywords: Venetoclax, AML, Allogeneic stem cell transplant, Hypomethylating agents